Expression of a viral gene in insulin-producing cell lines renders them susceptible to immunological destruction.

The gene coding for the glycoprotein D of herpes simplex virus type 1 was cloned into plasmids under the transcriptional control of the SV40 promoter-enhancer or the rat insulin 1 promoter-enhancer sequences. These plasmids were transfected into rat insulinoma cells (RINm5F) and mouse NIH/3T3 cells and the expression of glycoprotein D was examined using cell surface immunofluoresence. The rat insulin 1 promoter-enhancer sequences directed efficient expression in RINm5F cells, but not in NIH/3T3 cells. In contrast, the SV40 promoter-enhancer sequences worked well in NIH/3T3 cells, but not in RINm5F cells. Expression of glycoprotein D did not interfere with insulin production by RINm5F cells. When stable cel lines expressing glycoprotein D were exposed to anti-herpes simplex virus type 1 antibodies and complement, they were destroyed. These studies provide additional evidence that specific promoter-enhancer elements are required for efficient gene expression in certain cell types and demonstrate that the expression of foreign antigens on the surface of insulin-producing cells can lead to their immunological destruction.